The overall goal of this Center is to further our understanding of the neural network central to obsessive compulsive disorder (OCD) and the abnormalities within that network that are associated with the disease. Specifically, we will use a multimodal, network approach to: 1. localize specific regions and the pathways that connect them that are altered in the disease; 2. determine the effects of neuromodulation on the connectivity of the circuit(s); and 3. use these data to develop a non-invasive approach for individualized treatment. To understand the network underlying OCD, we use a multidimensional approach combining anatomy (structural analysis at the neuronal level) with global patterns of activity and connectivity (diffusion and functional MRI) to characterize the critical connections that underlie functional abnormalities in the OCD circuit, and the network changes following neuromodulation. Our central hypothesis is that OCD is characterized by hyperconnectivity between the amygdala/ventromedial prefrontal cortex and dorsal anterior cingulate (dACC) and orbitofrontal cortex (OFC), and decreased connectivity between dACC/OFC and dorsolateral and ventrolateral prefrontal cortex. This change in balance between emotion and cognitive control systems results in a heightened activity state in the dorsal striatum. We also posit that the structural basis for abnormalities in activity center aroun specific cortical regions (or nodes) that connect emotion-associated regions with those involved in cognitive control. Furthermore, we predict variability in the position of these nodes across individuals. Finally, we hypothesize that modulation of the circuit will return connectivity profils to relatively normal levels. The studies will provide a translational link to probe novel therapeutc targets. As this network has been linked to a wide range of psychiatric disorders including, depression, post-traumatic stress disorder, addictions, the resulting data will have implications that extend well beyond OCD.